P1388: A SINGLE-ARM, PROSPECTIVE MULTICENTER CLINICAL STUDY OF RELATED HLA HAPLOIDENTICAL PERIPHERAL BLOOD HEMATOPOIETIC STEM CELL TRANSPLANTATION WITHOUT IN VITRO T-CELL DEPLETION FOR HEMATOLOGICAL MALIGNAN
Authors: H. Yuan, S. Wang, J. Li, H. Bai, B. Zhang, C. Wang, L. Liu, L. Su, M. Jiang
Journal: HemaSphere (2022)

Background: Although haplo-HSCT has made great progress, how to better improve engraftment, reduce infection、GVHD and relapse incidence still requires continuous research. We believe that haplo-HSCT requires a higher dose of hematopoietic stem cells to solve the problem of engraftment and immune reconstitution, which is difficult to achieve simply by harvesting bone marrow as graft. To solve this problem, we designed a protocol using a high-dose PBSC without T-cell depleted in vitro as graft to undergo MAC haplo-PBSCT.Since 2004, our center has been carrying out this protocol to treat hematological malignancies. The primary engraftment was very good, the incidence rate of 100-day severe aGVHD was not high. PFS and OS are similar to those of other transplant centers at home or abroad. On this basis, to validate this protocol, we regisrered a voluntary single-arm, prospective multi-center clinical study in China. The incidence of 100-day aGVHD is the primary endpoint.From 2014 to 2019,a total of 8 hematopoietic stem cell transplantation centers in tertiary hospitals participated in this prospective multi-center clinical study. Aims: Taking aGVHD as the primary endpoint, engraftment, relapse rate, PFS and OS as the secondary endpoints. To verify the safety and feasibility of our unique haplo-PBSCT protocol. Methods: Haplo-PBSCT is based on ATG, ABuCy as a conditioning regimen, an intensive GVHD conditioning regimen containing anti-CD25 monoclonal antibody and early application of glucocorticoids, and enhanced infection prevention and control,without in vitro T-cell depletion, high-dose peripheral blood MNC infusion. Results: 102 haplo-PBSCT patients, 1 patient had primary failure of engraftment, and 3 patients had platelet non-engraftment. The median of transplanted MNC was 14.3 (8.2-27.8) × 108/kg, and the median of CD34+ cells was 8 (3.96-21.00) × 106/kg. The follow-up ended on January 31, 2022, and the median follow-up time was 66 (1-112) months. All patients could be assessed for aGVHD. 56 cases developed aGVHD, with a cumulative incidence of 52.8%. The cumulative incidence of aGVHD of grade II-IV was 25.1%, the cumulative incidence of grade III-IV aGVHD was 12.4%, the cumulative incidence of aGVHD in 27 standard-risk patients was 48.1%, and the aGVHD in 75 high-risk patients was 43.4%; 97 evaluable patients, 49 patients developed cGVHD, the 3-year cumulative incidence of cGVHD was 55%, the cumulative incidence of localized cGVHD was 46%, and the cumulative incidence of extensive cGVHD was 14.3%.The 3-year cumulative recurrence rate was 27.1%. The cumulative recurrence rates of ALL, AML, and MDS patients were 38.2%, 23.9%, and 16%, respectively. A total of 35 cases died, 10 cases of severe pulmonary infection, 4 cases of multiple organ failure (MOF), 2 cases of cerebral hemorrhage, and 19 cases of recurrence and death. The 3-year expected overall OS of AML, ALL and MDS patients was 72.7%, 57.1% and 58.3%, respectively. Image:Summary/Conclusion: This study shows that the severe aGVHD of our unique haplo-PBSCT is not high, which is comparable to the other ATG-based research datas. The relative long term follow-up observation indicates that a better clinical efficacy is achieved, the incidence of viral infection and recurrence of hematological malignancies are lower.